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The Grail of Calorie Restriction Benefits Without the Calorie Restriction


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#1 reason

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Posted 27 February 2015 - 12:51 AM


Seeking to recreate the benefits of calorie restriction - greater health and longer life - without the part of the process wherein you must eat less is a grail for modern medical research. The calorie restriction response is of greater benefit to basically healthy people than that produced by any currently available medical technology. Putting forward the idea that people should eat fewer calories is not a popular position in this modern age of comparatively wealth and comfort, however. It is entirely reasonable to expect that any new medicine that safely produced even a sizable fraction of the long term health improvements and slowing of aging triggered by the practice of calorie restriction would make a great deal of money. Thus there is a willingness in the research and development community to invest large amounts in scientific programs that have a chance of making this happen. Based on the pace of progress over the past two decades we shouldn't expect this grail to materialize any time soon, however. Calorie restriction changes near everything that can be measured in the operation of metabolism, and picking apart the complexity of this response costs billions and years even for a tiny slice of progress in understanding. Look at the history of sirtuin research, for example: a lot of hype at the outset, and nothing to show for it today but very expensive knowledge, a tiny addition to a vast catalog yet to be written.

Nonetheless the grail continues to attract attention. To the extent that this draws new funding into human life science research, this is all to the good: there's no such thing as too much life science research. Recreating calorie restriction isn't, however, an effective path to rejuvenation. It's just another way to tinker with the operation of metabolism to gently slow down the damage of aging. This is not particularly helpful to the old, who are already heavily damaged, and if takes decades for the research community to get anywhere, as seems most likely, it is not all that helpful to today's middle aged folk either. Research will always move forward, and tomorrow will be better than today, but it is very important that rejuvenation research aimed at dramatically cutting the rate of death and disease caused by aging moves as rapidly as possible to as beneficial an outcome as possible. Hundreds of millions of lives are the cost of a few years of delay. Calorie restriction mimetic development is a poor, expensive path. We should be focused on repair based strategies like SENS instead, those capable of producing rejuvenation and greatly extended healthy life spans as an outcome.

All things considered practicing calorie restriction now is a great plan. You can do it for next to nothing, and it has an expected beneficial effect considerably larger than any tinkering you can do with supplements and available medical technologies, assuming you're a basically healthy individual. Investing billions and decades and waiting for a drug that can do less for you than eating less? Not such a great plan. Decades and billions should be delivering far better results than that in terms of treatments for degenerative aging.

Here is news of work on a more recent approach to mimicking the effects of calorie restriction: it has become apparent that sensory neurons have a large effect on the calorie restriction response in lower animals, independent of actual calorie intake. This raises the possibility of some form of top-down manipulation in which at least some of the metabolic changes associated with calorie restriction are induced by altering the biochemistry of these sensory neurons. I should note that this is still all very early stage research, however. The grail is really no closer because of it.

Perception of food consumption overrides reality

The study focused on a molecule called AMP-activated protein kinase, or AMPK, which acts as a molecular fuel gauge to detect energy levels. It's been known that AMPK plays important roles in all cell types, but researchers didn't understand which of these activities were most critical to regulating longevity. The researchers found that AMPK inhibited the activity of a protein called CRTC-1 in neurons. This process, in turn, controlled the behavior of mitochondria - the primary energy-producing organelles in cells - throughout the organism, by altering production of a neurotransmitter.

The researchers were struck by the fact that altering the AMPK pathway in just a limited set of neurons was sufficient to override its effects on metabolism and longevity in other tissues. Aging was influenced more by what the animals perceived they were eating than what they actually ate. The study suggests that manipulating this energy-sensing pathway can cause organisms to perceive their cells to be in a low-energy state, even if they are eating normally and energy levels are high. Drugs targeting the cells' energy-sensors in this way could potentially address age-related diseases, including cancer and neurodegeneration, and may offer an alternative to calorie restriction.

Neuronal CRTC-1 Governs Systemic Mitochondrial Metabolism and Lifespan via a Catecholamine Signal

Low energy states delay aging in multiple species, yet mechanisms coordinating energetics and longevity across tissues remain poorly defined. The conserved energy sensor AMP-activated protein kinase (AMPK) and its corresponding phosphatase calcineurin modulate longevity via the CREB regulated transcriptional coactivator (CRTC)-1 in C. elegans. We show that CRTC-1 specifically uncouples AMPK/calcineurin-mediated effects on lifespan from pleiotropic side effects by reprogramming mitochondrial and metabolic function. This pro-longevity metabolic state is regulated cell nonautonomously by CRTC-1 in the nervous system. Targeting central perception of energetic state is therefore a potential strategy to promote healthy aging.

View the full article at FightAging

#2 Multivitz

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Posted 22 December 2015 - 12:16 AM

I like the last sentence, they mean the bodies photonic system I think.




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